Neurons Lose Their “Adaptability” in Old Age

 Will your competent? doctor notify you immediately of protocols created from this so you can benefit? 

OH NO! Knows nothing AND does nothing!

And your board of directors is so incompetent they can't recognize incompetence in their hospital!

Neurons Lose Their “Adaptability” in Old Age

Summary: Every thought has a price tag. Neurons require an immediate burst of energy to fire, but as we age, the brain’s “metabolic efficiency” begins to decline. Researchers have launched a five-year, $3.3M NIH-funded project to build the first whole-brain theory on how this metabolic cost impacts cognitive decline.

By looking beyond traditional “amyloid plaques,” the team is using advanced multiscale modeling—from single-cell mouse data to human MRIs—to identify how metabolites like glucose, lactate, and creatine predict the onset of Alzheimer’s Disease years before symptoms appear.

Key Facts

• The “Metabolic Cost” Theory: Neuronal activity is inextricably linked to energy consumption. When the brain can no longer adapt its metabolic processing to compensate for aging, cognitive decline begins.
• Beyond Amyloid: While most research focuses on protein plaques, this study targets the “neurometabolic coupling”—the relationship between blood flow, oxygen, and nutrient consumption in brain networks.
• Multiscale Modeling: The project spans three biological levels:
  1. Microscopic: Red blood cell velocity and lactate transients in mice.
  2. Mesoscopic: Mitochondrial activity rippling across cortical networks.
  3. Macroscopic: Whole-brain functional connectivity in human cohorts via MRI.
• The Translation Challenge: A major goal is to bridge the “mouse-to-human” gap. Scientists have “cured” Alzheimer’s in mice many times; this model aims to identify common metabolic vulnerabilities that actually apply to human patients.(Glad to see that they are accounting for rodent inflammation is not the same as human inflammation?)

• Predictive Screening: The ultimate aim is to create a screening tool that identifies at-risk individuals based on metabolic signals decades before memory loss occurs.

Source: University of Pittsburgh

Like a lightbulb illuminating the moment you flip a switch, the brain pays an immediate energy cost every time a neuron fires. Bistra Iordanova has built her career studying brain function, but over time, she kept returning to a question her field hadn’t fully investigated: how does this “cost” of the brain’s metabolism impact how we age? 

“I’ve collected lots of data about blood flow and the brain’s neuronal activity,” Iordanova said. “I eventually included data on glucose, lactate, creatine, and other brain metabolites in relation to aging, and then one morning, I found myself with so much information that I really had no clue what was going on. Simple linear models no longer worked, and dimensionality reduction approaches were not as useful as I hoped.”

Researchers are collaborating to build integrative neuro-metabolic models that can predict brain health across different species and life stages. Credit: Neuroscience News

For Iordanova, assistant professor of bioengineering at the University of Pittsburgh’s Swanson School of Engineering, that influx of data set the stage for an interdisciplinary collaboration with Liang Zhan, associate professor of electrical and computer engineering, to build integrative neuro-metabolic models capable of making predictions about brain health.

Now, the duo is co-investigating a five-year, $3.3M R01 NIH project, “Multiscale Models of Age-Specific Neurometabolic Coupling,” to create a whole-brain theory on how the brain’s metabolic processes affect cognition in aging. 

Looking beyond blood flow

While most research has typically focused on amyloid plaques and hemodynamics as early warning signs of Alzheimer’s Disease (AD), Iordanova and Zhan are focused on the metabolic changes that happen in the brain’s networks by looking at the impact of specific metabolites like glucose, lactate, and creatine on brain activity.

“The brain requires large amounts of glucose and oxygen to function as billions of interconnected cells work together,” Iordanova said. “But old age brings decline in metabolic efficiency, and our brain cells have to maintain networks by adapting their metabolic processing.” 

When that metabolic adaptation fails, it can lead to cognitive decline and dementia, and some individuals may be especially vulnerable due to genetics, lifestyle, or other factors. Ultimately, the goal of this work is to support the development of metabolic screening and therapies for at-risk individuals years before energy metabolism begins to affect cognition. First, however, the team must use advanced modeling strategies to make sense of the vast amount of metabolic and neural brain data they will collect.

A multi-scale, multi-species model

This approach will span three distinct levels of biological scale. At the smallest level, they will use two-photon microscopy to quantify the relationship between red blood cell velocity, neural activity, and lactate transients in late-onset AD mouse models.

Next, wide-field imaging will capture how mitochondrial activity ripples across cortical networks in mice. At the largest scale, the team will explore the impact of metabolism on functional whole-brain connectivity by integrating data from brain MRI in both animal models and human cohorts. 

“We want to connect what we know in mice on a cellular level to what we know from non-invasive imaging in humans,” Iordanova said. “And to build a comprehensive brain network theory, we need a lot of robust information at different scales.”

Once the data is collected at each step, Zhan will use his expertise in brain network modeling and graph theory to build the computational architecture that ties these complicated layers of brain data together. 

“The structures of mouse and human brains differ, and of course, we know that the brain is highly complex,” Zhan said. “Because many brain regions function together, diseases such as Alzheimer’s affect not just a single region but the entire brain network, which we aim to characterize and understand.”

Toward better treatments through interdisciplinary collaboration 

The ultimate goal of the project is to bridge the long-standing gap between discoveries in the laboratory and treatments that benefit patients. Although researchers have plenty of AD data from mouse models, translating those insights to humans remains a challenge.

By studying how metabolic factors interact with genetics, sex-differences and aging, the team hopes to identify biological signals that could eventually guide more personalized approaches to preventing cognitive decline.

“I’m obsessed with figuring out how to translate what we learn in mouse models of Alzheimer’s into something meaningful for humans, because translation is not trivial,” Iordanova said.

“A frequent quip on the translation from mouse to human is that scientists have cured Alzheimer’s in mice many times, but patients and families are still living through the disease every day. If we can improve on the cross-species approach to identify common metabolic vulnerabilities combined with certain genetic risk factors, then perhaps we could tailor interventions at the right time to the people who would benefit most.”

Although they now collaborate closely, Iordanova and Zhan were not previously familiar with each other’s work or the potential of their combined expertise until a chance meeting at a radiology event just a few years ago. While the research itself is promising, the team also hopes their partnership will encourage more engineers and scientists from different fields to pursue collaborative projects together. 

“Engineers and scientists from different fields often speak very different technical languages, and it’s rare to see those perspectives truly come together,” Iordanova said. “There’s real value when you are actually in the room with someone from another field and working to bridge that gap, and I think that’s what’s really valuable about this collaboration.”

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The interdisciplinary team also includes co-investigators Alberto Vazquez, Tao Jin and Alex Poplawsky from the School of Medicine and Nicholas Fitz and Rebecca Deek from the School of Public Health at University of Pittsburgh.

Funding: This project is supported by the National Institute on Aging (R01AG092661) for the period January 2026 through December 2030.

Key Questions Answered:

Q: Why focus on “energy” instead of the “plaques” we always hear about in Alzheimer’s?

A: Amyloid plaques are often the result of the disease, not necessarily the first spark. Iordanova believes metabolic changes happen much earlier. If the brain’s “power grid” starts failing, the cells can’t clean up waste or communicate properly, which may lead to those plaques forming later.

Q: Does this mean we can “eat” our way to a younger brain?

A: While diet affects glucose and lactate, this research is about how the brain processes those fuels. As we age, our cells become less efficient at turning glucose into “thought.” The goal is to find therapies that help aging neurons maintain their “metabolic flexibility” regardless of fuel supply.

Q: Why is it so hard to translate mouse research to humans?

A: Mice have different brain structures and shorter lifespans. By using “graph theory” and complex network modeling, Liang Zhan is building a mathematical “bridge” that can look at mouse cellular data and human MRI data side-by-side to find the universal rules of brain aging.

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Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this sleep and neuroscience research news

Author: Anna Ligorio
Source: University of Pittsburgh
Contact: Anna Ligorio – University of Pittsburgh
Image: The image is credited to Neuroscience News

NIGELLA SATIVA SEED OIL MITIGATES LIPOPOLYSACCHARIDES-INDUCED NEURODEGENERATION AND COGNITIVE IMPAIRMENT IN MICE

Don't do anything with this until human testing is done.

Who amongst your stroke medical 'professionals' can look at this and see that human testing needs to be done while also accounting for rodent inflammation is not the same as human inflammation?

Or don't you have anymore smart enough to see this?

NIGELLA SATIVA SEED OIL MITIGATES LIPOPOLYSACCHARIDES-INDUCED NEURODEGENERATION AND COGNITIVE IMPAIRMENT IN MICE

• Olusegun
• Gladys Adeoluwa
• Elizabeth Akinluiyi
• Juliet Olayinka
• Funmilayo Adeniyi
• Lily Otomewo

Open AccessDOI:https://doi.org/10.1016/j.ibneur.2023.08.657

Background: 

The hallmark of neurodegenerative diseases, such as Alzheimer’s disease, is chronic neuroinflammation. Nigella sativa seed oil popularly called black seed oil (BSO) is known for its anti-inflammatory and antioxidant properties. However, the mechanisms of its neuroprotective effect against neuroinflammation-induced neurodegeneration and memory dysfunction has not fully been explored. We thus evaluated its neuroprotective effect on lipopolysaccharides (LPS)-induced neurodegeneration and cognitive dysfunction in mice.

Outline of Material and Methods: Twenty-eight Swiss mice were assigned into four groups (n=7): group1 (vehicle), group2 (BSO 0.5mL/kg), group3 (Donepezil/5mg/kg), group4 (vehicle). Animals in different groups were administered with vehicle, BSO and donepezil for fourteen days. Starting from day 8, sixty-minutes after administration of vehicle/BSO/donepezil, animals in groups 2, 3 and 4, received LPS (500µg/kg, i.p.) consecutively for seven days. Twenty-four hour after treatment on day fourteen, Novel Object Recognition, (NORT) Y-maze, were used to assess cognitive functions; elevated plus maze, open field and light and dark box tests were used to assess anxiety. Tumor necrosis factor-α (TNF-α), interlukin-1β, acetylcholinesterase were assessed using ELISA technique, microglia, beta-amyloid, choline acetyltransferase (ChaT), synaptophysin, were quantified using immunohistochemistry, gene expressions of IL-10 and β-secretase were measured with quantitative Polymerase Chain Reaction. Cox Golgi staining technique was used to evaluate hippocampal damage.

Results: LPS significantly impaired performance in the Y-maze and NORT and induced behavioural abnormalities, compared to control. These were all ameliorated by treatment with BSO. BSO also significantly (P<0.05) reduced LPS-induced pro-inflammatory cytokines, acetylcholinesterase and expressions of microglia and β-secretase/mRNA in hippocampus and prefrontal cortex. In addition, BSO increased expressions of IL-10/mRNA gene, ChaT, synaptophysin in hippocampus and PFC. BSO significantly (P<0.05) decreased neurodegeneration of dendrite and neuronal cells in the hippocampus of LPS-treated mice.

Conclusion: Our results suggest that BSO may possess neuroprotective effect against LPS-induced neurodegeneration and cognitive impairment via mechanisms involving its anti-inflammatory properties.

Declaration of Interest Statement: None

Article info

Identification

DOI: https://doi.org/10.1016/j.ibneur.2023.08.657

Link Between High Blood Pressure, Immune System, and Cognitive Decline Revealed

Since you don't tell us what is high blood pressure, this is completely fucking useless!

Blood pressure before or after treatment? Simple questions you didn't bother to answer, so I'll be firing you. You don't explain how this might affect humans since

rodent inflammation is not the same as human inflammation?

The latest crapola here:

Link Between High Blood Pressure, Immune System, and Cognitive Decline Revealed

Summary: Immune system cells’ response in the brain’s protective covering may contribute to cognitive decline in individuals with chronic high blood pressure. New research provides insights into new ways to counteract high blood pressure’s impact on cognition.

Hypertension affects over a billion people globally, and this study found that immune cells’ abnormal activation in the brain leads to cognitive impairment. The findings highlight the importance of understanding the connection between immune signaling, blood pressure, and cognitive function.

Key Facts:

1. High blood pressure affects cognitive function even when stroke is not present.
2. Abnormal immune cell activation in the brain due to hypertension contributes to cognitive decline.
3. The study suggests that targeting overactive immune cells in the brain could be a potential treatment approach.

Source: NIH

A study supported by the National Institutes of Health suggests that the response of immune system cells inside the protective covering surrounding the brain may contribute to the cognitive decline that can occur in a person with chronic high blood pressure.

This finding, published in Nature Neuroscience, may shed light on new ways to counteract the effects of high blood pressure on cognition.

The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

Once in the brain, IL-17 turned on immune cells responsible for activating inflammation and fighting off infections, known as macrophages. Credit: Neuroscience News

“The role of immune signaling in cognitive decline is critically important to understand,” said Roderick Corriveau, Ph.D., program director, NINDS. “These findings offer insight into how signaling from the immune system could contribute to symptoms of cognitive decline that ultimately result in dementia diagnoses.”

Hypertension affects more than 1 billion people worldwide and can lead to a decline in cognitive function including when a stroke occurs, but also even when a person with high blood pressure does not have a stroke. However, efforts to control cognitive loss in people who do not experience a stroke with treatments that lower blood pressure have shown mixed results.

The findings of this mouse study suggest that immune cells around and within the brain become abnormally activated under conditions that mimic a common form of hypertension, and this activation leads to impaired brain function.

Using a mouse model of high blood pressure, the researchers led by Costantino Iadecola, M.D., director and chair of the Feil Family Brain and Mind Research Institute, New York City, found abnormally increased levels of interleukin-17 (IL-17), a chemical normally released in the body to activate the immune system, in the cerebral spinal fluid and the brain.

Previously, Dr. Iadecola’s team showed that a high salt diet increased IL-17 in the gut, which was followed by cognitive impairment. These new findings add to that story by showing that IL-17 is acting within the brain itself. It’s also notable that these experiments use a different mouse model, called the DOCA salt model, that more closely mimics a common form of hypertension in people.

“This is currently the most realistic model of hypertension that we have,” said Dr. Iadecola. “The DOCA mouse simulates low-renin hypertension, which is a common type of hypertension in people, particularly among Black Americans.”

Further work showed that, once in the brain, IL-17 turned on immune cells responsible for activating inflammation and fighting off infections, known as macrophages.

A series of experiments confirmed that these macrophages are important for the observed decline in cognition, as both mice in which the receptor for IL-17 was deleted in brain macrophages and those that had their brain macrophages depleted showed no effects of high blood pressure on cognitive function despite having other symptoms of hypertension.

Researchers still sought the source of the IL-17 acting on the brain macrophages. Based on their previous work, the researchers’ initial hypothesis was that the gut releases IL-17, which then travels to the brain through the blood stream. Once there, it sets off a reaction that damages the ability of brain blood vessels to respond appropriately to increased brain activity.

However, blocking the brain blood vessels’ ability to respond to IL-17 only partially rescued cognitive impairment, suggesting that there was another source of IL-17 acting on the brain.

One clue came from other recent studies suggesting that one layer of the protective covering of the brain, known as dura mater, contains immune T cells that can both secrete IL-17 and can affect the behavior of mice.

Using special mice where cells light up fluorescent green when they make IL-17, the researchers confirmed that hypertension increases IL-17 in the dura mater which is then released into the tissue.

Normally, barriers exist within the protective covering of the brain, called the meninges, to prevent unwanted spillage into the brain. However, this barrier appeared to be disrupted in the mice with experimentally induced hypertension, and this disruption allowed IL-17 to enter the cerebral spinal fluid.

Two additional experiments helped to confirm this hypothesis. First, a drug was used to prevent T cell movement from the lymph nodes into the meninges. Second, an antibody was used to block the activity of T cells in the meninges. In both cases, cognitive function was restored in the mice with hypertension, suggesting that targeting overactive T cells could be a new treatment approach worth exploring.

“Together, our data suggest two different effects are caused by hypertension,” said Dr. Iadecola.

“One is IL-17 acting on blood vessels, but this appears to be relatively minor. A more prominent, central effect is caused by cells in the meninges releasing IL-17 that directly affects immune cells in the brain. It is these immune cells, activated by signaling from the meninges, that ultimately affect the brain in a way that causes cognitive impairment.”  

Dr. Iadecola and his team are now looking to connect the dots between the activation of immune cells in the meninges and decreased cognitive function. 

Previous work by the group suggested a connection between a high salt diet which suppressed the production of the chemical nitric oxide in brain vessels that in turn led to buildup of tau, a toxic protein that forms clumps in neurons affected by Alzheimer’s disease.

The present findings also show suppression of nitric oxide production within brain vessels, and whether this also leads to an increase in tau production is currently under investigation.

The NINDS’s Mind Your Risks® campaign serves to highlight the connection between high blood pressure and brain health (including risk of stroke and dementia), particularly among Black men ages 28-45, and offers strategies to prevent and mitigate high blood pressure’s effects on brain health.

Funding: This study was funded by NINDS (NS089323, NS095441, NS123507), the Leon Levy Fellowship in Neuroscience, and the Feil Family Foundation.   

About this neurology research news

Author: Carl Wonders
Source: NIH
Contact: Carl Wonders – NIH
Image: The image is credited to Neuroscience News

Original Research: Closed access.
“Meningeal IL-17 producing T cells mediate cognitive impairment in salt-sensitive hypertension” by Santisteban MM et al. Nature Neuroscience

Molecular Treatment Helps Mice Regain Brain Function After Stroke

Who amongst your stroke medical 'professionals' can look at this and see that human testing needs to be done while also accounting for rodent inflammation is not the same as human inflammation?

Or don't you have anymore smart enough to see this?

Do you prefer your  doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

Molecular Treatment Helps Mice Regain Brain Function After Stroke

A class of small molecules has been shown to help mice regain brain function after a stroke.

News  

Published: December 4, 2023

 

| Original story from Lund University

Credit: Anna Shvets/ Pexels

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Researchers have succeeded in restoring lost brain function in mouse models of stroke using small molecules that in the future could potentially be developed into a stroke recovery therapy. “Communication between nerve cells in large parts of the brain changes after a stroke and we show that it can be partially restored with the treatment”, says Tadeusz Wieloch, senior professor of neurobiology at Lund University in Sweden.

“Concomitantly, the rodents regain lost somatosensory functions, something that around 60 per cent of all stroke patients experience today. The most remarkable result is that the treatment began several days after a stroke,” Wieloch continues. 

In an ischemic stroke, lack of blood flow to the brain causes damage, which rapidly leads to nerve cell loss that affects large parts of the the vast network of nerve cells in the brain. This may lead to loss of function such as paralysis, sensorimotor impairment and vision and speech difficulties, but also to pain and depression. There are currently no approved drugs that improve or restore the functions after a stroke, apart from clot-dissolving treatment in the acute phase (within 4.5 hours of the stroke). Some spontaneous improvements occur, but many stroke patients suffer chronic loss of function. For example, about 60 per cent of stroke sufferers, experience lost somatosensori functions such as touch and position sense.

An international study published recently in the journal Brain and led by a research team from Lund University in collaboration with University of Rome La Sapeinza and Washington University at St. Louis, shows promising results in mice and rats that were treated with a class of substances that inhibit the metabotropic glutamate receptor (mGluR5), a receptor that regulates communication in the brain’s nerve cell network. 

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“Rodents treated with the GluR5 inhibitor regained their somatosensori functions,” says Tadeusz Wieloch, who led the study published in BRAIN.

Two days after the stroke, i.e. when the damage had developed and function impairment was most prominent, the researchers started treating the rodents that exhibited the greatest impaired function.

“A temporary treatment effect was seen after just 30 minutes, but treatment for several weeks is needed to achieve a permanent recovery effect. Some function improvement was observed even when the treatment started 10 days after a stroke,” says Tadeusz Wieloch.

Importantly, sensorimotor functions improved, even though the extent of the brain damage was not diminished. This, explains Tadeusz Wieloch, is due to the intricate network of nerve cells in the brain, known as the connectome, i.e. how various areas of the brain are connected and communicate with each to form the basis for various brain functions.

“Impaired function after a stroke is due to cell loss, but also because of reduced activity in large parts of the connectome in the undamaged brain. The receptor mGluR5 is apparently an important factor in the reduced activity in the connectome, which is prevented by the inhibitor which therefore restores the lost brain function,” says Tadeusz Wieloch.

The results also showed that sensorimotor function was further improved if treatment with the mGluR5 inhibitor is combined with somatosensory training by housing several rodents in cages enriched with toys, chains, grids, and plastic tubes.

The researchers hope that in the future their results could lead to a clinical treatment that could be initiated a few days after an ischemic stroke.

“Combined with rehabilitation training, it could eventually be a new promising treatment. However, more studies are needed. The study was conducted on mice and rats, and of course needs to be repeated in humans. This should be possible since several mGluR5 inhibitors have been studied in humans for the treatment of neurological diseases other than stroke, and shown to be tolerated by humans,” says Tadeusz Wieloch.

Reference: Hakon J, Quattromani MJ, Sjölund C, et al. Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity. Brain. 2023:awad293. doi: 10.1093/brain/awad293

Whistleblowers and former lab members suggest star neuroscientist Berislav Zlokovic may have manipulated data that support a major stroke trial and important Alzheimer’s research

 FYI.

Do these people even know that rodent inflammation is not the same as human inflammation? Which was the whole starting point of this research.

• 3K3A-APC (6 posts to August 2012)

Whistleblowers and former lab members suggest star neuroscientist Berislav Zlokovic may have manipulated data that support a major stroke trial and important Alzheimer’s research

A version of this story appeared in Science, Vol 382, Issue 6672.Download PDF

In 2022, the U.S. National Institutes of Health (NIH) placed a large bet on an experimental drug developed to limit brain damage after strokes. The agency committed up to $30 million to administer a compound called 3K3A-APC in a study of 1400 people shortly after they experience an acute ischemic stroke, a perilous condition in which a clot blocks blood flow to part of the brain.

The gamble seemed warranted. Lab studies, most by a longtime grantee, prominent University of Southern California (USC) neuroscientist Berislav Zlokovic, had generated promising data. A small safety study of the drug, sponsored by a company Zlokovic co-founded called ZZ Biotech, was also encouraging. Analyses of data from the phase 2 trial hinted that the treatment reduced the number of tiny, asymptomatic brain hemorrhages after stroke patients received either surgery to remove the clot, the clot-busting drug tissue plasminogen activator (tPA), or both.

For many years, scientists have tried to reduce the brain cell death, bleeding, and inflammation that can follow a stroke, some of which results from disruption of the blood-brain barrier—a system of tiny blood vessels that delivers oxygen and nutrients but shields the brain from toxic substances. tPA, the only approved stroke drug in the United States and Europe, can vastly reduce death and disability by clearing a stroke’s blockage, but the drug, too, can cause dangerous brain bleeding. 3K3A-APC could help mitigate such damage and prevent brain cells from dying, ZZ Biotech said.

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Because of its potential to address an unmet medical need, the U.S. Food and Drug Administration (FDA) gave the compound “fast track” status, with the prospect of “accelerated approval and priority review.” ZZ Biotech says the new trial should start within a few months.

But a 113-page dossier obtained by Science from a small group of whistleblowers paints a less encouraging picture. The dossier, which they submitted to NIH, highlights evidence from the phase 2 trial that the experimental remedy might have actually increased deaths in the first week after treatment: Six of the 66 stroke patients who received 3K3A-APC died within this period, compared with one among 44 in the placebo group, although the death rate evened out after a month. Patients who received the drug also trended toward greater disability and dependency at the end of the trial, 90 days after treatment.

Deepening the concern, the dossier also highlights evidence that dozens of papers from Zlokovic’s lab—including many supporting the idea that the compound was ready for human testing—contain seemingly doctored data that suggest scientific misconduct. The whistleblowers say apparent changes to images used for protein identification and other purposes seem to skew results in favor of the scientist’s hypotheses, which include influential ideas about the blood-brain barrier and its role in stroke and Alzheimer’s disease, as well as how 3K3A-APC supposedly affects it.

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Zlokovic’s institution, USC, will confidentially review the content of the dossier, a spokesperson said, adding, “USC takes any allegations relating to research integrity seriously.” Zlokovic declined requests for an interview about the whistleblowers’ findings. But an attorney representing him told Science in a statement that Zlokovic “is committed to fully cooperating” with the USC inquiry. Without providing specifics, the statement noted that some elements of the dossier are “based on information and premises Professor Zlokovic knows to be completely incorrect,” or pertain to experiments not completed in his lab.

But speaking to Science anonymously, four former members of Zlokovic’s lab say the anomalies the whistleblowers found are no accident. They describe a culture of intimidation, in which he regularly pushed them and others in the lab to adjust data. Two of them said he sometimes had people change lab notebooks after experiments were completed to ensure they only contained the desired results. “There were clear examples of him instructing people to manipulate data to fit the hypothesis,” one of the lab members says.

I immediately felt nauseous. … The integrity of the scientific record is so fundamental to what we do that seeing this kind of data anomaly is distressing.

• Chris Schaffer
• Cornell Univers